Triethylamine → HCID 68527287, compound

HRID 884153Notes

Reaction equation

HRID 884153 reaction equation
[NH2:1][C:2]1[CH:3]=[CH:4][C:5]([O:8][C:9]2[CH:19]=[CH:18][C:12]([C:13]([O:15]CC)=O)=[CH:11][CH:10]=2)=[N:6][CH:7]=1.C(N(CC)CC)C.[Cl:27][C:28]1[CH:29]=[C:30]([CH:34]=[CH:35][C:36]=1[Cl:37])[C:31](Cl)=[O:32].[OH-].[Na+].[CH2:40]([N:48]1[CH2:53][CH2:52][NH:51][CH2:50][CH2:49]1)[CH2:41][C:42]1[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=1.Cl.C(N=C=NCCCN(C)C)C.O.ON1C2C=CC=CC=2N=N1>C1COCC1>[Cl:27][C:28]1[CH:29]=[C:30]([CH:34]=[CH:35][C:36]=1[Cl:37])[C:31]([NH:1][C:2]1[CH:7]=[N:6][C:5]([O:8][C:9]2[CH:10]=[CH:11][C:12]([C:13]([N:51]3[CH2:52][CH2:53][N:48]([CH2:40][CH2:41][C:42]4[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=4)[CH2:49][CH2:50]3)=[O:15])=[CH:18][CH:19]=2)=[CH:4][CH:3]=1)=[O:32]

Participants

9

Reactant 7

HCID 8471TriethylamineHCID 14798Sodium HydroxideHCID 76403Benzoyl chloride, 3,4-dichloro-HCID 792141-PhenethylpiperazineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 68523649HCID 68523649, compound

Product 1

HCID 68527287HCID 68527287, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of ethyl 4-(5-aminopyridin-2-yloxy)benzoate (690 mg, 2.7 mmol) in THF (10 mL) were added triethylamine (0.73 mL, 5.3 mmol) and 3,4-dichlorobenzoyl chloride (570 mg, 2.7 mmol) under ice cooling, and the resulting solution was stirred for 1 hour under ice cooling. This reaction solution was concentrated under reduced pressure, and to the residue was added ethyl acetate. The resulting solution was washed with water, 1 N hydrochloric acid and brine, and then dried over anhydrous magnesium sulfate. The solvent was evaporated, and the residue was washed, when hot, with n-hexane:dichloromethane=1:2. The product was dissolved in THF (20 mL). To the residue was added 1 N aqueous sodium hydroxide (2.9 mL, 2.9 mmol), and this solution was stirred for 5 hours at 100° C. THF was evaporated, and the aqueous layer was made to have a pH of 3 with 1 N hydrochloric acid. Precipitated matter was collected by filtration, and dried. The resulting product was dissolved in bMF (10 mL), and 1-phenethylpiperazine (200 mg, 1.1 mmol), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (240 mg, 1.3 mmol) and 1-hydroxybenzotriazole monohydrate (170 mg, 1.3 mmol) were added to the solution. The resulting solution was stirred for 1 day at room temperature. This reaction solution was concentrated under reduced pressure, and to the residue was added chloroform. The resulting solution was washed with water, and then dried over anhydrous magnesium sulfate. The solvent was evaporated, and the residue was purified by silica gel column chromatography (methanol:chloroform=1:99), to thereby yield 310 mg of the title compound.

Workup

  1. concentrationThis reaction solution was concentrated under reduced pressure
  2. additionto the residue was added ethyl acetate
  3. washThe resulting solution was washed with water, 1 N hydrochloric acid and brine
  4. dry with materialdried over anhydrous magnesium sulfate
  5. customThe solvent was evaporated
  6. washthe residue was washed
  7. dissolutionThe product was dissolved in THF (20 mL)
  8. stirringthis solution was stirred for 5 hours at 100° C
  9. customTHF was evaporated
  10. customPrecipitated matter
  11. filtrationwas collected by filtration
  12. customdried
  13. additionwere added to the solution
  14. stirringThe resulting solution was stirred for 1 day at room temperature
  15. concentrationThis reaction solution was concentrated under reduced pressure
  16. additionto the residue was added chloroform
  17. washThe resulting solution was washed with water
  18. dry with materialdried over anhydrous magnesium sulfate
  19. customThe solvent was evaporated
  20. customthe residue was purified by silica gel column chromatography (methanol:chloroform=1:99)

Sources & evidence

ORD record
ord-21a88c4de3444dfa90bdb8f8fe4d79e5
Source dataset
uspto-grants-2012_08
Patent number
US08236826B2

Reaction notes

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